The long-range purpose of this project is initially to study the immunologic aspects of the factor VIII/von Willebrand factor protein, and then to study the biochemistry and structure of this protein in man. The topics of present interest are: 1) the defect of the factor VIII/von Willebrand factor protein in hemophilia A; 2) the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease; 3) the importance of carbohydrate content in biological functions; 4) the relationship of carbohydrate content to atherosclerosis; 5) the mechanism of thrombin activation, and 6) biochemical characterization of the biologically active sites of the factor VIII/von Willebrand factor protein.